In this project we have demonstrated that CD34+ progenitor cells can maintain engrafting function after ex vivo expansion. Importantly, cultured cells can decrease the neutropenia experienced by animals after CD34+ stem cell transplantation. This biological effect requires the administration of growth factors to the recipient animal after transplantation. We have expanded our studies to include progenitors in the developing fetus. In these studies we find that fetal CD34+ progenitors are present in high frequency in the circulation during the second trimester of fetal development. Human and baboon fetal progenitors are biologically very similar with regard to phenotype, in vitro growth properties, changes during fetal development, and susceptibility to retrovirus-mediated gene transfer. We plan to extend our studies to transplantation of autologous fetal progenitors in baboons as a model for fetal hematopoietic stem cell gene therapy. FUNDING NIH grants RR00166, AI35191, CA15704, AI37747 and HL54881 and Amgen Corp. McSweeney, P.A., Rouleau, K.A., Wallace, P.M., Bruno, B., Andrews, R.G., Srizanac-Bengez, L., Sandmaier, B.M., Storb, R., Wayner, E., and Nash, R.A. Characterization of monoclonal antibodies that recognize canine CD34. Blood 91:1977-1986, 1998. Shields, L.E. and Andrews, R.G. Gestational age changes in circulating CD34+ hematopoietic stem/progenitor cells in fetal cord blood. Am. J. Obstet. Gynecol. 178:931-937, 1998. Opie, T., Shields, L.F., and Andrews, R.G. Cell surface antigen expression in early and term gestation fetal hematopoietic progenitor cells. Stem Cells 16 343-348, 1998.